Abstract While highly active antiretroviral therapy (HAART) has significantly improved the health of individuals infected with human immunodeficiency virus-1 (HIV), available therapeutics largely target virus replication pathways such that treatment interruption results in the rapid resumption of viral replication and decline of immunologic function. Even despite successful therapeutic control of replication, chronic inflammation, HIV-associated neurocognitive disorders, cardiovascular disease and other comorbidities further threaten the health of an estimated 1.2 million HIV-infected people in the U.S. New therapeutic strategies capable of longer term virus suppression and reductions in the sources of persistent virus would relieve consequences of daily drug compliance and comorbidities for over 34 million HIV-infected people globally. Jericho Sciences? investigational small molecule, FX101, is proposed to target the highly conserved zinc finger domains of lentiviral nucleocapsid (NC) proteins, a well-established therapeutic target for the treatment of HIV. FX101 has demonstrated preclinical safety and antiviral efficacy in multiple in vivo, ex vivo and in vitro models to support continuing translational testing. Zinc finger domains (ZFDs) of HIV nucleocapsid (NC) protein are highly conserved therapeutic targets shared across all lentiviruses, including feline, simian and human immunodeficiency viruses (FIV, SIV and HIV, respectively). Following eight monotherapeutic doses of FX101 over four weeks in chronically FIV-infected cats ? one of the research models for HIV ? blood plasma and cerebrospinal fluid viremia remained 85-95% below corresponding pretreatment levels up to 36 weeks following cessation of treatment, in the absence of observed or measured adverse events (p<0.0005; n=6; one-way ANOVA). These results are unprecedented in FIV-infected cats. Concurrently, integrated provirus in peripheral blood mononuclear cells continued to decrease by 95% from the normalized starting virus load (p<0.0001; n=6; one-way ANOVA). While we have yet to fully elucidate mechanistic implications of the nucleocapsid target profile, the most differentiating feature is the potential long term control of virus production in an apparent systemic reduction of virus replication setpoint. We propose here to conduct translational testing of FX101 in a simian immunodeficiency virus-infected nonhuman primate (SIV/NHP) model to establish the safety profile, therapeutic efficacy, and clinical biomarkers that may implicate this strategic candidate molecule?s potential utility toward a cotherapeutic functional eradication of HIV infection in humans. .